The use of chemotherapy in treating children with newly diagnosed ependymoma is currently being investigated, both clinically and experimentally. Assessment of the true efficacy of this modality is hampered by a lack of prospective randomized trials comparing conventional treatment schemes of aggressive surgical excision followed by radiation therapy with or without addition of chemotherapy. Although with current regimens, the role of chemotherapy in newly diagnosed disease appears limited, measurable disease responses have been recognized. Preliminary studies support the potential use of chemotherapy in infants in an effort to delay radiation therapy or even avoid radiation therapy, although with conventional chemotherapy, a delay exceeding 12 months is inadvisable. Additionally, preliminary data suggest that in children with incompletely resected tumors, chemotherapy may be of benefit as an adjunct to second-look surgery. Experimental work investigating chemotherapeutic sensitivity, molecular genetics, or mechanisms to overcome drug resistance may offer some benefit in utilizing chemotherapy for ependymoma of childhood.